Clinical Trials Register

Summary
EudraCT Number:	2013-002050-78
Sponsor's Protocol Code Number:	NVALT-21
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-07-09
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2013-002050-78

A.3

Full title of the trial

A Phase III, randomised trial of adding nitroglycerin to first line chemotherapy for advanced nonsmall cell lung cancer

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A trial of adding nitroglycerin tochemotherapy for advanced lung cancer

A.3.2

Name or abbreviated title of the trial where available

NITRO TRIAL

A.4.1

Sponsor's protocol code number

NVALT-21

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NVALT
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Koningin Wilhelmina Fonds
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NVALT
B.5.2	Functional name of contact point	principal investigator
B.5.3	Address:
B.5.3.1	Street Address	Luijbenstraat 15
B.5.3.2	Town/ city	's-Hertogenbosch
B.5.3.3	Post code	5211 BR
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3173612 61 63 na
B.5.5	Fax number	nananana
B.5.6	E-mail	secretariaat@nvalt.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Transiderm Nitro 25 mg 10 cm2
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Transiderm-Nitro 5
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tansiderm-Nitro
D.3.9.1	CAS number	55-63-0
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	NITROGLYCERIN
D.3.9.4	EV Substance Code	SUB37490
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

advanced non-small cell lung cancer

E.1.1.1

Medical condition in easily understood language

metastatic lung cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10059515
E.1.2	Term	Non-small cell lung cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Progression-free survival

E.2.2

Secondary objectives of the trial

1. Overall survival (OS)
2. Objective tumour response rates (OTRR)
3. Adverse events (AE)
4. Health-related quality of life (HRQL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically or cytologically confirmed diagnosis of a stage III or IV non-small cell lung carcinoma
(including cytology obtained by brushings, washings or needle aspirations; and/or sputum cytology
positive on at least 2 occasions). Patients with stage III disease must not be candidates for subsequent
surgery and/or chemoradiotherapy) [Refer to Appendix 3]. Measurable disease is not required.
2. ECOG performance status of 0, 1 or 2 at the time of randomisation [Appendix 4].
3. Adequate bone-marrow, renal and hepatic function as follows:
Haemoglobin ≥ 100 g/l
Absolute neutrophil count ≥1.5 x 109/L
Platelet count ≥100 x 109/L
Serum bilirubin ≤1.5 times ULN (Upper Limit of Normal)
Alanine transaminase (ALT) ≤2.5 times ULN if liver metastases not evident <5 times
ULN if liver metastases are evident
Serum creatinine ≤1.5 times (ULN)
or
Calculated creatinine clearance ≥ 50ml/min
4. Radiotherapy completed at least 1 week before randomisation (a 3-week gap is recommended for
radiation including significant volumes of lung or bone marrow).
5. The patient is willing and able to comply with the requirements of the protocol and will be accessible for
follow-up
6. Has completed the HRQL questionnaires or is unable to complete them because of illiteracy,
insufficient english, or limited vision.
7. Patient is >18 years of age.
8. If the patient is female, then she must be either of non-childbearing potential (i.e. be post-menopausal,
or have a current tubal ligation, hysterectomy or oophorectomy) or if of childbearing potential, then she
must practice adequate contraception for 30 days prior to administration of study treatment, have a
negative pregnancy test (serum or urine) and continue such precautions during all study treatment
period and for 2 months after completion of chemotherapy.
9. Written informed consent
10. Plan to start chemotherapy within 8 days of randomisation

E.4

Principal exclusion criteria

1. Untreated brain or meningeal metastases
2. Life expectancy less than 3 months.
3. Any prior systemic therapy for advanced non-small lung cancer including cytotoxic drugs, anti EGF or
anti VEGF drugs. Adjuvant chemotherapy for non-small cell lung cancer completed more than 12
months before randomisation is allowed.
4. History of previous or concomitant malignancies at other sites within the last 5 years. Exceptions:
Effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated
malignancy that has been in remission for over 5 years and highly likely to have been cured.
5. On nitrates, dihydroergotamine or phosphodiesterase inhibitors (e.g. sildenafil)
6. History of allergic disease or reactions likely to be exacerbated by nitroglycerin.
7. Uncontrolled cardiovascular disease, including symptomatic congestive cardiac failure, symptomatic
coronary artery disease, or clinically significant hypotension.
8. Other concurrent medical problems, unrelated to the malignancy, which would limit compliance with the
study procedures or expose the patient to unacceptable risk.
9. Active and uncontrolled infections
10. Psychiatric or addictive disorders that may compromise their ability to give informed consent, or to
comply with the trial procedures.
11. Any investigational or non-registered medicinal product within the 30 days preceding the first dose of
study medication, or plans to receive such a drug during the study period.
12. For female patients: the patient is pregnant or lactating.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (time from randomisation to progression or death, primary endpoint)

E.5.1.1

Timepoint(s) of evaluation of this end point

Continuously

E.5.2

Secondary end point(s)

1. Overall survival (time from randomisation to death from any cause)
2. Frequency of complete response, partial response, and stable disease at 6 months according to
RECIST 1.1 (see Appendix 5). 68
3. Patients’ ratings of HRQL with the EORTC QLQ-C30, QLQ-LC13, UBQ-C, Patient DATA Form,
and EQ5-D (see Appendix 7).
4. Clinicians’ ratings of patients with Spitzers’ Quality of Life Index (see Appendix 7), ECOG
performance scale (see Appendix 4).
5. Adverse events categorised and graded according to NCI Common Terminology Criteria for
Adverse Events v3.0. (See Appendix 6).
6. Compliance, duration of therapy and reasons for discontinuation expressed in terms of:
o numbers of cycles of chemotherapy completed
o duration of study treatment and reasons for stopping
o dose-intensity of given chemotherapeutics.

E.5.2.1

Timepoint(s) of evaluation of this end point

Continuously

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

New Zealand

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last patient last visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

150

F.4.2.2

In the whole clinical trial

500

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-07-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-01-10

P. End of Trial
P.	End of Trial Status	Ongoing

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